Functional and phenotypic analysis of thymic CD34(+)CD1a(-) progenitor-derived dendritic cells: Predominance of CD1a(+) differentiation pathway

Whether thymic dendritic cells (DC) are phenotypically and functionally dis tinct from the monocyte lineage DC is an important question. Human thymic p rogenitors differentiate into T, NK, and DC. The latter induce clonal delet ion of autoreactive thymocytes and therefore might be different from their monocyte-derived counterparts. The cytokines needed for the differentiation of DC from thymic progenitors were also questioned, particularly the need for GM-CSF, We show that various cytokine combinations with or without GM-C SF generated DC from CD34(+)CD1a(-) but not from CD34(+)CD1a(+) thymocytes, CD34(+) thymic cells generated far fewer DC than their counterparts from t he cord blood. The requirement for IL-7 was strict whereas GM-CSF was dispe nsable but nonetheless improved the yield of DC. CD14(+) monocytic intermed iates were not detected in these cultures unless macrophage-CSF (M-CSF) was added. Cultures in M-CSF generated CD14(-)CD1a(+) DC precursors but also C D14(+)CD1a(-) cells, When sorted and recultured in GM-CSF, CD14(+) cells do wn-regulated CD14 and up-regulated CD1a. TNF-alpha accelerated the differen tiation of progenitors into DC and augmented MHC class D transport to the m embrane, resulting in improved capacity to induce MLR, The trafficking of M HC class II molecules was studied by metabolic labeling and immunoprecipita tion, MHC class II molecules were transported to the membrane in associatio n with invariant chain isoforms in CD14(+) (monocyte)-derived and in CD1a() thymic derived DC but not in monocytes, Thus, thymic progenitors can diff erentiate into PC along a preferential CD1a(+) pathway but have conserved a CD14(+) maturation capacity under M-CSF, Finally, CD1a(+)-derived thymic D C and monocyte-derived DC share very dose Ag-proeessing machinery.